6,6'-bi(5-hydroxytryptamine-4,7-dione) | 124620-49-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 6,6'-bi(5-hydroxytryptamine-4,7-dione)
• CAS: 124620-49-1
• 化学式: C₂₀H₁₈N₄O₆
• 分子量: 410.386
• InChiKey: JQHCZQGRSQDATC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.43
• 重原子数：
  30.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  192.36
• 氢给体数：
  6.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  3-(2-氨基乙基)-1H-吲哚-5,7-二醇 在 phosphate buffer 、 氧气 作用下， 反应 2.0h， 生成 5-hydroxytryptamine-4,7-dione 、 6,6'-bi(5-hydroxytryptamine-4,7-dione)
  参考文献：
  名称：

  血清素神经毒素5,7-二羟基色胺的自氧化作用。

  摘要：

  吲哚神经毒素5,7-二羟基色胺（5,7-DHT）已被广泛认为可表达其神经变性，这是由于神经内自氧化作用引起的。直到最近，据信自氧化作用导致使神经元膜蛋白烷基化的反应性亲电醌亚胺种类，而自氧化反应的副产物是细胞毒性的还原氧种类。这项研究表明，在生理pH值下，5,7-DHT的碳负离子充当主要的电子给体，以1：2的比例生成以C（4）和C（6）为中心的自由基超氧化物复合物。以C（4）为中心的复合物反应生成最终的5-羟基色胺-4,7-二酮，该物质已被证明比5,7-DHT具有更强大的神经毒素。以C（6）为中心的自由基超氧化物络合物反应生成6,6'-双（5-羟基色胺4）7-dione）。后者反应很可能产生O2-作为细胞毒性副产物。

  DOI：

  10.1021/jm00164a032

文献信息

• Chemical and enzyme-mediated oxidation of the serotonergic neurotoxin 5,7-dihydroxytryptamine: mechanistic insights
  作者：Tahereh Tabatabaie、Glenn Dryhurst

  DOI：10.1021/jm00090a018

  日期：1992.6

  Because of its enormous basicity O2- facilitates deprotonation of 1. The C(4)-centered carbanion so produced is oxidized by molecular O2 or by the hydroperoxy radical (HO2) to give radical intermediates and thence 2 and 3. Mechanistic pathways leading to the various products of oxidation of 1 are proposed and the potential roles of oxidation reactions of the indolamine are related to its neurodegenerative

  在生理pH条件下，在厌氧和好氧条件下，研究了5-羟色胺神经毒素5,7-二羟基色胺（1）的氧化化学和生物化学。在厌氧条件下，单电子氧化剂（铁细胞色素c，过氧化物酶/ H2O2，铜蓝蛋白，Cu2 +）产生自由基中间体。此自由基的C（6）中心共振形式的二聚反应，然后进行二次氧化，生成3-（2-氨基乙基）-6- [3-（2-氨基乙基）-1,7-二氢-5-羟基-7-氧代-6H-吲哚-6-亚烷基] -1-H-吲哚-5,7（4H，6H）-二酮。在有氧条件下，分子O2攻击以C（4）为中心的1自由基，产生氢过氧自由基，该自由基分解为5-羟基色胺-4,7-二酮（2）。1的自动氧化过程由分子O2对以C（4）为中心的碳负离子的主要攻击进行，从而形成超氧化物自由基复合物。这重新排列成一个以C（4）为中心的氢过氧化物，它分解为2。以AC（6）为中心的碳负离子与1相结合，最终得到6,6'-bi-5-hydroxytryptamine-4
• Further insights into the molecular mechanisms of action of the serotonergic neurotoxin 5,7-dihydroxytryptamine
  作者：Tahereh Tabatabaie、R. N. Goyal、C. LeRoy Blank、Glenn Dryhurst

  DOI：10.1021/jm00054a006

  日期：1993.1

  Autoxidation and various enzyme-mediated oxidations of the serotonergic neurotoxin 5,7-dihydroxytryptamine (1) give 5-hydroxytryptamine-4,7-dione (2) and 6,6'-bi(5-hydroxytryptamine-4,7-dione) (3) as the major products. When administered into the ventricular system of mice 2 and 3 are general toxins. The LD50 values for 2 (29.6 +/- 0.04 mug) and 3 (25.4 +/- 0.30 mug) are lower than that for 1 (51.8 +/- 0.28 mug). In the presence of cellular reductants (glutathione, cysteine, ascorbate) and molecular oxygen, or when incubated with rat brain homogenate, 2 and 3 redox cycle and form superoxide radical anion, O2.-, as a byproduct. The lethal effects of 2 and 3 when introduced into the brain may in part be due to such redox cycling reactions which deplete oxygen levels and, as a result of Haber-Weiss chemistry deriving from O2.-, form the cytotoxic hydroxyl radical (HO.). Intraventricular administration of 2 and 3 to mice causes only relatively minor and transient (ca. 1 h to 1 day) changes in whole brain levels of dopamine, 5-hydroxytryptamine (from both 2 and 3), acetylcholine, and choline (from 2 only). These changes differ from the profound and long-lasting serotonergic deficit evoked by 1. On the basis of these results a hypothesis has been formulated which proposes that the selective neurotoxicity of 1 derives from its rapid uptake into serotonergic neurons where it is oxidatively converted to 2 and 3. Redox cycling reactions of 2 and 3 then result in the depletion of intraneuronal oxygen and concomitant formation of O2.-. Dismutation of O2.-gives H2O2 which, as a result of transition metal ion-catalyzed Haber-Weiss chemistry, yields HO.. Thus, neuronal damage and death might result from the combined effects of hypoxia and HO. formation.
• TABATABAIE, TAHEREH;WRONA, MONIKA Z.;DRYHURST, GLENN, J. MED. CHEM., 33,(1990) N, C. 667-672
  作者：TABATABAIE, TAHEREH、WRONA, MONIKA Z.、DRYHURST, GLENN

  DOI：——

  日期：——